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Toward understanding the outer membrane uptake of small molecules by Pseudomonas aeruginosa.

ABSTRACT: Because small molecules enter Gram-negative bacteria via outer membrane (OM) channels, understanding OM transport is essential for the rational design of improved and new antibiotics. In the human pathogen Pseudomonas aeruginosa, most small molecules are taken up by outer membrane carboxylate channel (Occ) proteins, which can be divided into two distinct subfamilies, OccD and OccK. Here we characterize substrate transport mediated by Occ proteins belonging to both subfamilies. Based on the determination of the OccK2-glucuronate co-crystal structure, we identify the channel residues that are essential for substrate transport. We further show that the pore regions of the channels are rigid in the OccK subfamily and highly dynamic in the OccD subfamily. We also demonstrate that the substrate carboxylate group interacts with central residues of the basic ladder, a row of arginine and lysine residues that leads to and away from the binding site at the channel constriction. Moreover, the importance of the basic ladder residues corresponds to their degree of conservation. Finally, we apply the generated insights by converting the archetype of the entire family, OccD1, from a basic amino acid-specific channel into a channel with a preference for negatively charged amino acids.

SUBMITTER: Eren E

PROVIDER: S-EPMC3636890 | biostudies-literature | 2013 Apr

REPOSITORIES: biostudies-literature

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Toward understanding the outer membrane uptake of small molecules by Pseudomonas aeruginosa.

Eren Elif E Parkin Jamie J Adelanwa Ayodele A Cheneke Belete B Movileanu Liviu L Khalid Syma S van den Berg Bert B

The Journal of biological chemistry 20130306 17

Because small molecules enter Gram-negative bacteria via outer membrane (OM) channels, understanding OM transport is essential for the rational design of improved and new antibiotics. In the human pathogen Pseudomonas aeruginosa, most small molecules are taken up by outer membrane carboxylate channel (Occ) proteins, which can be divided into two distinct subfamilies, OccD and OccK. Here we characterize substrate transport mediated by Occ proteins belonging to both subfamilies. Based on the deter ...[more]

PMID: 23467408

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Toward understanding the outer membrane uptake of small molecules by Pseudomonas aeruginosa.

Publications

Toward understanding the outer membrane uptake of small molecules by Pseudomonas aeruginosa.

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